ArticleLaboratory investigation; a journal of technical methods and pathology2010
The protective role of pregnane X receptor in lipopolysaccharide/D-galactosamine-induced acute liver injury.
Article in Laboratory investigation; a journal of technical methods and pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Prevention of D-GalN/LPS-induced ALI by 18β-glycyrrhetinic acid through PXR-mediated inhibition of autophagy degradation.Cell death & disease · 2021Article
- Deletion or inhibition of SphK1 mitigates fulminant hepatic failure by suppressing TNFα-dependent inflammation and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Pregnane X Receptor Activation Triggers Rapid ATP Release in Primed Macrophages That Mediates NLRP3 Inflammasome Activation.The Journal of pharmacology and experimental therapeutics · 2019Article
- Betulinic acid attenuates liver fibrosis by inducing autophagy via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.Journal of natural medicines · 2019Article
- Bone marrow mesenchymal stem cell-derived exosomes attenuate D-GaIN/LPS-induced hepatocyte apoptosis by activating autophagy in vitro.Drug design, development and therapy · 2019Article
- Diet-induced obesity impairs spermatogenesis: a potential role for autophagy.Scientific reports · 2017Article
- The Protective Effect of Cordycepin on D-Galactosamine/Lipopolysaccharide-Induced Acute Liver Injury.Mediators of inflammation · 2017Article
- Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation.The Journal of pharmacology and experimental therapeutics · 2016Article
- [Role of autophagy in acute liver failure induced by D-galactosamine/lipopolysaccharide in mice].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2016Article
- Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies.Nature reviews. Drug discovery · 2016Review
- Inhibition of glycogen synthase kinase 3β promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor α.Cell death & disease · 2016Article
- Exaggerated IL-15 and Altered Expression of foxp3+ Cell-Derived Cytokines Contribute to Enhanced Colitis in Nlrp3-/- Mice.Mediators of inflammation · 2016Article
- Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity.Nuclear receptor research · 2016Article
- Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury.PloS one · 2016Article
- Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4.Immunity · 2014Article
- Adenosine 5'-monophosphate ameliorates D-galactosamine/lipopolysaccharide-induced liver injury through an adenosine receptor-independent mechanism in mice.Cell death & disease · 2014Article
- Liver autophagy in anorexia nervosa and acute liver injury.BioMed research international · 2014Review
- Expression of the PXR gene in various types of cancer and drug resistance.Oncology letters · 2013Article
- Targeting the pregnane X receptor in liver injury.Expert opinion on therapeutic targets · 2012Review
- Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure.Hepatobiliary & pancreatic diseases international : HBPD INT · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The pregnane X receptor (PXR) is a nuclear receptor transcription factor regulating drug-metabolizing enzymes and transporters that facilitate xenobiotic and endobiotic detoxification. Recent studies show that PXR is important in abrogating intestinal tissue damage. This study examines the role of PXR in lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced acute liver injury using wild-type and PXR-null mice. LPS/GalN-treated PXR-null mice had greater increases of alanine transaminase (ALT), hepatocyte apoptosis, necrosis, and hemorrhagic liver injury than wild-type mice. LPS/GalN-mediated phosphorylation of JNK1/2 and ERK1/2 was differentially regulated in wild-type and PXR-null mice. Importantly, LPS/GalN-induced hepatic Stat3 survival signaling was impaired and early activation of Jak2 was delayed in PXR-null mice. Expression levels of pro-survival proteins Bcl-xL and heme oxygenase-1 (HO-1), which are downstream of Stat3, were substantially lower in PXR-null than wild-type mouse livers after LPS/GalN treatment. Autophagy is also involved in LPS/GalN-induced liver injury. Lack of PXR resulted in a significant reduction of LC3B-I, -II as well as Beclin-1 protein levels after LPS/GalN treatment. In addition, PXR is implicated in hepatocytes homeostasis. Taken together, PXR is a critical hepatoprotective factor. Increases of LPS/GalN-induced hepatocyte apoptosis and liver injury in PXR-null mice are due to deregulated mitogen-activated protein (MAP) kinase activation as well as delayed Jak2/Stat3 activation, which lead to a compromise in defense mechanisms that involve Bcl-xL-, HO-1, and autophagy-mediated pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.